Regulation of ribosomal RNA gene copy number and its role in modulating genome integrity and evolutionary adaptability in yeast.

Kobayashi T - Cell. Mol. Life Sci. (2011)

Bottom Line:
Due to their repetitive structure and highly active transcription, the rRNA gene repeats are some of the most fragile sites in the chromosome.In addition, we recently found that the repeat number determines sensitivity to DNA damage.In this review, I would like to introduce a new aspect of the rRNA gene repeat (called rDNA) as a center of maintenance of genome integrity and discuss its contribution to evolution.

ABSTRACTThe genes encoding ribosomal RNA (rRNA) are the most abundant genes in the eukaryotic genome. They reside in tandem repetitive clusters, in some cases totaling hundreds of copies. Due to their repetitive structure and highly active transcription, the rRNA gene repeats are some of the most fragile sites in the chromosome. A unique gene amplification system compensates for loss of copies, thus maintaining copy number, albeit with some fluctuations. The unusual nature of rRNA gene repeats affects cellular functions such as senescence. In addition, we recently found that the repeat number determines sensitivity to DNA damage. In this review, I would like to introduce a new aspect of the rRNA gene repeat (called rDNA) as a center of maintenance of genome integrity and discuss its contribution to evolution.

Fig5: The rDNA theory for aging. The rDNA is one of the most unstable regions in the genome. Therefore, its instability affects cellular functions. rDNA instability a directly reduces cellular functions through dysfunction of ribosomes, b activates the damage checkpoint control that reduces cellular functions through elongation of cell cycle, c sequesters repair enzymes, resulting in the instability of non-rDNA regions and d the instability of non-rDNA regions reduces cellular functions through the checkpoint control and dysfunction of important genes (see [1])

Mentions:
How rDNA instability leads to cellular senescence is still unknown. One possibility is that unstable rDNA changes the effective concentrations of some proteins, such as repair enzymes. In fact, mutants in DNA repair genes are known to have a shorter lifespan in yeast and human cells [25, 26]. Moreover, aged cells often show genome instability [27]. Therefore, one possible model for the mechanism by which rDNA instability promotes aging is that (1) rDNA instability leads to an accumulation of repair enzymes at the locus because of more recombinational events, (2) The effective free concentration of these factors drops, and as a result, stability of the genome as a whole is reduced, (3) The damage checkpoint control is activated. This reduces cellular functions by blocking the cell cycle, and finally, (4) cells stop growing (Fig. 5, see review [1]).Fig. 5

Fig5: The rDNA theory for aging. The rDNA is one of the most unstable regions in the genome. Therefore, its instability affects cellular functions. rDNA instability a directly reduces cellular functions through dysfunction of ribosomes, b activates the damage checkpoint control that reduces cellular functions through elongation of cell cycle, c sequesters repair enzymes, resulting in the instability of non-rDNA regions and d the instability of non-rDNA regions reduces cellular functions through the checkpoint control and dysfunction of important genes (see [1])

Mentions:
How rDNA instability leads to cellular senescence is still unknown. One possibility is that unstable rDNA changes the effective concentrations of some proteins, such as repair enzymes. In fact, mutants in DNA repair genes are known to have a shorter lifespan in yeast and human cells [25, 26]. Moreover, aged cells often show genome instability [27]. Therefore, one possible model for the mechanism by which rDNA instability promotes aging is that (1) rDNA instability leads to an accumulation of repair enzymes at the locus because of more recombinational events, (2) The effective free concentration of these factors drops, and as a result, stability of the genome as a whole is reduced, (3) The damage checkpoint control is activated. This reduces cellular functions by blocking the cell cycle, and finally, (4) cells stop growing (Fig. 5, see review [1]).Fig. 5

Bottom Line:
Due to their repetitive structure and highly active transcription, the rRNA gene repeats are some of the most fragile sites in the chromosome.In addition, we recently found that the repeat number determines sensitivity to DNA damage.In this review, I would like to introduce a new aspect of the rRNA gene repeat (called rDNA) as a center of maintenance of genome integrity and discuss its contribution to evolution.

ABSTRACTThe genes encoding ribosomal RNA (rRNA) are the most abundant genes in the eukaryotic genome. They reside in tandem repetitive clusters, in some cases totaling hundreds of copies. Due to their repetitive structure and highly active transcription, the rRNA gene repeats are some of the most fragile sites in the chromosome. A unique gene amplification system compensates for loss of copies, thus maintaining copy number, albeit with some fluctuations. The unusual nature of rRNA gene repeats affects cellular functions such as senescence. In addition, we recently found that the repeat number determines sensitivity to DNA damage. In this review, I would like to introduce a new aspect of the rRNA gene repeat (called rDNA) as a center of maintenance of genome integrity and discuss its contribution to evolution.